Macrolide antibiotics are useful in the treatment of a broad spectrum of bacterial infections and protozoa infections in mammals, fish and birds. These antibiotics include derivatives of erythromycin A, some of which have been formed by the addition of naturally occurring intermediates of erythromycin biogenesis to the fermentation media of Streptomyces antibioticus ATCC 31771. Spagnoli, R., et al., J. Antibiotics, 34(4):365-375 (1983); U.S. Pat. No. 4,439,426. The resulting oleandrose derivatives are more stable than erythromycin A under acidic conditions.
Other derivatives of erythromycin A include azalides such as azithromycin, the synthesis of which is described by U.S. Pat. Nos. 4,474,768 and 4,517,359. The azalide aglycone contains a nitrogen atom and is structurally, conformationally and electronically distinct from naturally occurring macrolide aglycones. Prior to the invention, it was believed that biological cultures would not glycosilate this unnatural macrolide aglycone.